Predictive Factors and Baseline Risk Stratification for CAR-T Cell Therapy-Related Cardiovascular Toxicity.

Aims: Baseline cardiovascular (CV) risk stratification is an essential component in managing patients undergoing potential cardiotoxic anticancer therapies. Chimeric antigen receptor (CAR)-T cell therapy, a groundbreaking treatment for hematologic malignancies, is associated with a non-negligible risk of cardiovascular adverse events (CVAE). This study aimed to identify predictors of CAR-T cell-related CVAE and to develop a corresponding risk stratification score.

Methods: We conducted a meta-analysis of studies comparing baseline clinical, biomarker, echocardiographic findings, and pharmaceutical treatments between patients who developed CAR-T cell-related CVAE and those who did not. We subsequently used the pooled relative risks (RR) of significant predictors to construct a risk stratification score.

Results: We identified 12 relevant studies encompassing a total of 1354 patients with haematologic malignancies, the majority of which were treated with CD19-directed CAR-T cell therapy, of whom 228 (16.8%) developed CVAE. Significant predictors of CAR-T cell-related CVAE included coronary artery disease [RR = 2.27 (95% confidence interval, 1.46-3.51)], hyperlipidaemia [1.57 (1.14-2.15)], diabetes [1.59 (1.13-2.24)], hypertension [1.45 (1.18-1.77)], atrial fibrillation [2.42 (1.51-3.88)], heart failure [2.74 (1.62-4.61)], and smoking [1.40 (1.10-1.79)]. The resulting risk prediction score, incorporating the above seven factors, named CART-7, ranges from 0 to 33, with a score of 0-8 indicating low risk, 9-17 moderate risk, 18-25 high risk, and 26-33 very high risk.

Conclusion: Seven baseline CV conditions were significantly associated with CAR-T cell-related CVAE. Further validation of the resulting CART-7 score is warranted to support its clinical use in baseline CV risk stratification for patients undergoing CAR-T cell therapy.